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Assessing the neutralizing antibody and duration of RNA positivity from COVID-19 infected patients with immunocompromised diseases and pneumonia. 评估感染 COVID-19 的免疫功能低下疾病和肺炎患者的中和抗体和 RNA 阳性持续时间。
IF 6.3 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-28 DOI: 10.1186/s43556-024-00191-1
Shuo Liu, Xuelian Wu, Ziteng Liang, Weijin Huang, Yufeng Xiong
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引用次数: 0
UCHL5 is a putative prognostic marker in renal cell carcinoma: a study of UCHL family. UCHL5 是肾细胞癌的潜在预后标志物:对 UCHL 家族的研究。
IF 6.3 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-22 DOI: 10.1186/s43556-024-00192-0
Mengdi Zhang, Jingxian Li, Sijia Liu, Fangfang Zhou, Long Zhang

A macroscopic perspective is indispensable for understanding the intricate relationship between deubiquitinases and tumorigenesis. Proteomics has been proposed as a viable approach for elucidating the complex role of deubiquitylation in cellular progression. Instead of studying the function of a single ubiquitinase, research on a deubiquitinase family with similar catalytic core(s) may provide a new perspective for the pathological understanding of cancer. The Ubiquitin C-terminal hydrolase L (UCHL) family consists of four members: UCHL1, UCHL3, UCHL5, and BRAC1 associated protein-1 (BAP1), and they have been implicated in tumorigenesis and metastasis. Some members are considered hallmarks of intracranial lesions, colon cancer, chromatin remodeling, and histone stability. The present study uncovered an unknown correlation between the UCHL family and renal cancer. We discovered that UCHLs exhibit diverse regulatory effects in renal cancer, establishing connections between the renal cancer and truncated gene mutations, mitochondrial energetic metastasis, immune cell infiltration, and chromosomal stability of UCHLs family. Notably, we found that the increase of UCHL5 expression in renal cancer cells decreases the antigen processing and presentation of RCC tumor-infiltrating B cells. Further research identified that the expression of UCHL5 in RCC tumors is correlated with transport proteins, which led us to find that the abundance of UCHL5 in the blood of late-stage renal cell cancer patients is upregulated from 18 ng/L to 500 ng/L. Therefore, we propose that the abundance of UCHL5 in patients' blood can be a possible indicator of poor prognosis for renal cell cancer.

要了解去泛素化酶与肿瘤发生之间错综复杂的关系,宏观视角是必不可少的。蛋白质组学被认为是阐明去泛素化在细胞进展中的复杂作用的可行方法。与其研究单一泛素酶的功能,不如研究具有相似催化核心的去泛素酶家族,这可能会为癌症的病理研究提供一个新的视角。泛素 C 端水解酶 L(UCHL)家族由四个成员组成:UCHL1、UCHL3、UCHL5 和 BRAC1 相关蛋白-1 (BAP1),它们与肿瘤发生和转移有关。其中一些成员被认为是颅内病变、结肠癌、染色质重塑和组蛋白稳定性的标志。本研究发现了 UCHL 家族与肾癌之间未知的相关性。我们发现,UCHLs 在肾癌中表现出多种调控作用,并建立了肾癌与截短基因突变、线粒体能量转移、免疫细胞浸润和 UCHLs 家族染色体稳定性之间的联系。值得注意的是,我们发现肾癌细胞中 UCHL5 表达的增加会降低 RCC 肿瘤浸润 B 细胞的抗原处理和递呈能力。进一步的研究发现,UCHL5 在 RCC 肿瘤中的表达与转运蛋白相关,这使我们发现 UCHL5 在晚期肾细胞癌患者血液中的含量从 18 纳克/升升高至 500 纳克/升。因此,我们认为患者血液中 UCHL5 的含量可能是肾细胞癌预后不良的一个指标。
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引用次数: 0
m6A-dependent mature miR-151-5p accelerates the malignant process of HNSCC by targeting LYPD3. 依赖于 m6A 的成熟 miR-151-5p 通过靶向 LYPD3 加速了 HNSCC 的恶性进程。
IF 6.3 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-16 DOI: 10.1186/s43556-024-00189-9
Fei Huang, Yuan Ren, Yufei Hua, Ying Wang, Ruomeng Li, Ning Ji, Xin Zeng, Ding Bai, Qianming Chen, Xikun Zhou, Junjie Wu, Jing Li

miRNA has emerged as a crucial regulator in various of pathological and physiological processes, yet its precise mechanism of action the detailed mechanism of their action in Head and neck squamous cell carcinoma (HNSCC) remains incompletely understood. This study sheds light on the role of mi-151-5p, revealing its significantly elevated expression in tumor cells, which notably enhances the invasion and migration of HNSCC cells. This effect is achieved through directly targeting LY6/PLAUR Domain Containing 3 (LYPD3) by miR-151-5p, involving complementary binding to the 3'-untranslated regions (3'-UTR) in the mRNA of LYPD3. Consequently, this interaction accelerates the metastasis of HNSCC. Notably, clinical observations indicate a correlation between high expression of miR-151-5p and low levels of LYPD3 in clinical settings are correlated with poor prognosis of HNSCC patients. Furthermore, our investigation demonstrates that glycosylation of LYPD3 modulates its subcellular localization and reinforces its role in suppressing HNSCC metastasis. Additionally, we uncover a potential regulatory mechanism involving the facilitation of miR-151-5p maturation and accumulation through N6-methyladenosine (m6A) modification. This process is orchestrated by methyltransferase-like 3 (METTL3) and mediated by a newly identified reader, heterogeneous nuclear ribonucleoprotein U (hnRNP U). These findings collectively underscore the significance of the METTL3/miR-151-5p/LYPD3 axis serves as a prominent driver in the malignant progression of HNSCC.

miRNA 已成为各种病理和生理过程中的重要调节因子,但其确切的作用机制仍不完全清楚。本研究揭示了 mi-151-5p 在肿瘤细胞中的作用,发现它在肿瘤细胞中的表达明显升高,这显著增强了 HNSCC 细胞的侵袭和迁移。这种作用是通过 miR-151-5p 直接靶向 LY6/PLAUR Domain Containing 3 (LYPD3),与 LYPD3 mRNA 中的 3'- 非翻译区 (3'-UTR) 互补结合实现的。因此,这种相互作用加速了 HNSCC 的转移。值得注意的是,临床观察表明,miR-151-5p 的高表达和 LYPD3 的低水平与 HNSCC 患者的不良预后相关。此外,我们的研究表明,LYPD3 的糖基化可调节其亚细胞定位,并加强其抑制 HNSCC 转移的作用。此外,我们还发现了一种潜在的调控机制,即通过 N6-甲基腺苷(m6A)修饰促进 miR-151-5p 的成熟和积累。这一过程由类似甲基转移酶 3(METTL3)协调,并由新发现的阅读器异质核糖核蛋白 U(hnRNP U)介导。这些发现共同强调了METTL3/miR-151-5p/LYPD3轴在HNSCC恶性进展中的重要作用。
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引用次数: 0
Exploring haematopoietic stem cell dynamics through mitochondrial mutation profiling. 通过线粒体突变特征分析探索造血干细胞的动态变化。
IF 6.3 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-10 DOI: 10.1186/s43556-024-00190-2
Yongming Xia, Ruixiu Chen, Shiwei Duan
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引用次数: 0
Multiple myeloma: signaling pathways and targeted therapy. 多发性骨髓瘤:信号通路和靶向治疗。
IF 6.3 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-04 DOI: 10.1186/s43556-024-00188-w
Qizhong Lu, Donghui Yang, Hexian Li, Ting Niu, Aiping Tong

Multiple myeloma (MM) is the second most common hematological malignancy of plasma cells, characterized by osteolytic bone lesions, anemia, hypercalcemia, renal failure, and the accumulation of malignant plasma cells. The pathogenesis of MM involves the interaction between MM cells and the bone marrow microenvironment through soluble cytokines and cell adhesion molecules, which activate various signaling pathways such as PI3K/AKT/mTOR, RAS/MAPK, JAK/STAT, Wnt/β-catenin, and NF-κB pathways. Aberrant activation of these pathways contributes to the proliferation, survival, migration, and drug resistance of myeloma cells, making them attractive targets for therapeutic intervention. Currently, approved drugs targeting these signaling pathways in MM are limited, with many inhibitors and inducers still in preclinical or clinical research stages. Therapeutic options for MM include non-targeted drugs like alkylating agents, corticosteroids, immunomodulatory drugs, proteasome inhibitors, and histone deacetylase inhibitors. Additionally, targeted drugs such as monoclonal antibodies, chimeric antigen receptor T cells, bispecific T-cell engagers, and bispecific antibodies are being used in MM treatment. Despite significant advancements in MM treatment, the disease remains incurable, emphasizing the need for the development of novel or combined targeted therapies based on emerging theoretical knowledge, technologies, and platforms. In this review, we highlight the key role of signaling pathways in the malignant progression and treatment of MM, exploring advances in targeted therapy and potential treatments to offer further insights for improving MM management and outcomes.

多发性骨髓瘤(MM)是浆细胞恶性肿瘤中第二常见的血液恶性肿瘤,以溶骨性骨病变、贫血、高钙血症、肾功能衰竭和恶性浆细胞聚集为特征。MM 的发病机制涉及 MM 细胞与骨髓微环境之间通过可溶性细胞因子和细胞粘附分子的相互作用,从而激活各种信号通路,如 PI3K/AKT/mTOR、RAS/MAPK、JAK/STAT、Wnt/β-catenin 和 NF-κB 通路。这些通路的异常激活导致骨髓瘤细胞的增殖、存活、迁移和耐药性,使它们成为有吸引力的治疗干预靶点。目前,针对 MM 这些信号通路的获批药物非常有限,许多抑制剂和诱导剂仍处于临床前或临床研究阶段。MM 的治疗选择包括非靶向药物,如烷化剂、皮质类固醇、免疫调节药物、蛋白酶体抑制剂和组蛋白去乙酰化酶抑制剂。此外,单克隆抗体、嵌合抗原受体T细胞、双特异性T细胞啮合剂和双特异性抗体等靶向药物也被用于MM的治疗。尽管 MM 的治疗取得了重大进展,但这种疾病仍然无法治愈,这就强调了基于新兴理论知识、技术和平台开发新型或联合靶向疗法的必要性。在这篇综述中,我们强调了信号通路在 MM 恶性进展和治疗中的关键作用,探讨了靶向治疗和潜在治疗的进展,为改善 MM 的管理和预后提供了进一步的见解。
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引用次数: 0
Single-cell transcriptomic profiling reveals decreased ER protein Reticulon3 drives the progression of renal fibrosis. 单细胞转录组分析显示,ER 蛋白 Reticulon3 的减少推动了肾脏纤维化的进展。
IF 6.3 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-28 DOI: 10.1186/s43556-024-00187-x
Shuai Guo, Yi Dong, Ran Du, Yu-Xing Liu, Shu Liu, Qin Wang, Ji-Shi Liu, Hui Xu, Yu-Jie Jiang, Huang Hao, Liang-Liang Fan, Rong Xiang

Chronic kidney disease (CKD) poses a significant global health dilemma, emerging from complex causes. Although our prior research has indicated that a deficiency in Reticulon-3 (RTN3) accelerates renal disease progression, a thorough examination of RTN3 on kidney function and pathology remains underexplored. To address this critical need, we generated Rtn3-null mice to study the consequences of RTN3 protein deficiency on CKD. Single-cell transcriptomic analyses were performed on 47,885 cells from the renal cortex of both healthy and Rtn3-null mice, enabling us to compare spatial architectures and expression profiles across 14 distinct cell types. Our analysis revealed that RTN3 deficiency leads to significant alterations in the spatial organization and gene expression profiles of renal cells, reflecting CKD pathology. Specifically, RTN3 deficiency was associated with Lars2 overexpression, which in turn caused mitochondrial dysfunction and increased reactive oxygen species levels. This shift induced a transition in renal epithelial cells from a functional state to a fibrogenic state, thus promoting renal fibrosis. Additionally, RTN3 deficiency was found to drive the endothelial-to-mesenchymal transition process and disrupt cell-cell communication, further exacerbating renal fibrosis. Immunohistochemistry and Western-Blot techniques were used to validate these observations, reinforcing the critical role of RTN3 in CKD pathogenesis. The deficiency of RTN3 protein in CKD leads to profound changes in cellular architecture and molecular profiles. Our work seeks to elevate the understanding of RTN3's role in CKD's narrative and position it as a promising therapeutic contender.

慢性肾脏病(CKD)是一个严重的全球性健康难题,其产生原因复杂。尽管我们之前的研究表明,网状神经元3(RTN3)的缺乏会加速肾脏疾病的进展,但对RTN3对肾脏功能和病理影响的深入研究仍然不足。为了满足这一迫切需要,我们培育了Rtn3缺失小鼠,以研究RTN3蛋白缺乏对CKD的影响。我们对来自健康小鼠和 Rtn3 缺失小鼠肾皮质的 47,885 个细胞进行了单细胞转录组分析,比较了 14 种不同细胞类型的空间结构和表达谱。我们的分析表明,RTN3 缺乏会导致肾细胞的空间组织和基因表达谱发生显著改变,从而反映出慢性肾功能衰竭的病理变化。具体来说,RTN3 缺乏与 Lars2 过度表达有关,而 Lars2 过度表达又会导致线粒体功能障碍和活性氧水平升高。这种转变诱导肾上皮细胞从功能状态转变为纤维化状态,从而促进肾纤维化。此外,研究还发现 RTN3 缺乏会推动内皮细胞向间质转化过程,并破坏细胞间的交流,从而进一步加剧肾脏纤维化。免疫组化和Western-Blot技术被用来验证这些观察结果,从而加强了RTN3在CKD发病机制中的关键作用。CKD 中 RTN3 蛋白的缺乏会导致细胞结构和分子特征发生深刻变化。我们的工作旨在提高人们对 RTN3 在 CKD 中作用的认识,并将其定位为一种有前景的治疗方法。
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引用次数: 0
Inhibition of cysteine-serine-rich nuclear protein 1 ameliorates ischemia-reperfusion injury during liver transplantation in an MAPK-dependent manner. 抑制富含半胱氨酸-丝氨酸的核蛋白 1 能以 MAPK 依赖性方式改善肝移植过程中的缺血再灌注损伤。
IF 6.3 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-21 DOI: 10.1186/s43556-024-00185-z
Zhoucheng Wang, Wenwen Ge, Xinyang Zhong, Shizheng Tong, Shusen Zheng, Xiao Xu, Kai Wang

Hepatic ischemia-reperfusion injury (HIRI) is a critical pathophysiological process during liver transplantation (LT). Multiple genes and signal pathways are dysregulated during HIRI. This study aims to identify genes as potential therapeutic targets for ameliorating HIRI. Datasets containing samples from the human donor liver (GSE151648) and mouse HIRI model (GSE117066) were analyzed to determine differentially expressed genes (DEGs). The selected DEGs were confirmed by real-time PCR and western blot in the hepatocyte hypoxia-reoxygenation (HR) model, mouse HIRI model, and human liver samples after transplantation. Genetic inhibition was used to further clarify the underlying mechanism of the gene in vitro and in vivo. Among the DEGs, CSRNP1 was significantly upregulated (|log FC|= 2.08, P < 0.001), and was positively correlated with the MAPK signal pathway (R = 0.67, P < 0.001). CSRNP1 inhibition by siRNA significantly suppressed apoptosis in the AML-12 cell line after HR (mean Annexin+ ratio = 60.62% vs 42.47%, P = 0.0019), but the protective effect was eliminated with an additional MAPK activator. Knocking down CSRNP1 gene expression by intravenous injection of AAV-shRNA markedly reduced liver injury in mouse HIRI model (ALT: AAV-NC vs AAV-shCsrnp1 = 26,673.5 ± 2761.2 vs 3839.7 ± 1432.8, P < 0.001; AST: AAV-NC vs AAV-shCsrnp1 = 8640.5 ± 1450.3 vs 1786.8 ± 518.3, P < 0.001). Liver-targeted delivery of siRNA by nanoparticles effectively inhibited intra-hepatic genetic expression of Csrnp1 and alleviated IRI by reducing tissue inflammation and hepatocyte apoptosis. Furthermore, CSRNP1 inhibition was associated with reduced activation of the MAPK pathway both in vitro and in vivo. In conclusion, our results demonstrated that CSRNP1 could be a potential therapeutic target to ameliorate HIRI in an MAPK-dependent manner.

肝脏缺血再灌注损伤(HIRI)是肝移植(LT)过程中的一个关键病理生理过程。在肝缺血再灌注损伤过程中,多种基因和信号通路失调。本研究旨在确定作为潜在治疗靶点的基因,以改善 HIRI。研究人员分析了包含人类供体肝脏样本(GSE151648)和小鼠 HIRI 模型样本(GSE117066)的数据集,以确定差异表达基因(DEGs)。在肝细胞缺氧-复氧(HR)模型、小鼠 HIRI 模型和移植后的人类肝脏样本中,通过实时 PCR 和 Western 印迹证实了所选的 DEGs。通过基因抑制进一步阐明了该基因在体外和体内的潜在机制。在 DEGs 中,CSRNP1 明显上调(|log FC|= 2.08,P + ratio = 60.62% vs 42.47%,P = 0.0019),但使用额外的 MAPK 激活剂后,保护作用被消除。在小鼠 HIRI 模型中,通过静脉注射 AAV-shRNA 敲低 CSRNP1 基因表达明显减轻了肝损伤(ALT:AAV-NC vs AAV-shCsrnp1 = 26,673.5 ± 2761.2 vs 3839.7 ± 1432.8,P||=2.08)。
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引用次数: 0
Ckip-1 3'UTR alleviates prolonged sleep deprivation induced cardiac dysfunction by activating CaMKK2/AMPK/cTNI pathway. Ckip-1 3'UTR通过激活CaMKK2/AMPK/cTNI通路缓解长期睡眠剥夺诱发的心功能障碍。
IF 6.3 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-14 DOI: 10.1186/s43556-024-00186-y
Beilei Dong, Rui Xue, Jianwei Li, Shukuan Ling, Wenjuan Xing, Zizhong Liu, Xinxin Yuan, Junjie Pan, Ruikai Du, Xinming Shen, Jingwen Zhang, Youzhi Zhang, Yingxian Li, Guohui Zhong

Sleep deprivation (SD) has emerged as a critical concern impacting human health, leading to significant damage to the cardiovascular system. However, the underlying mechanisms are still unclear, and the development of targeted drugs is lagging. Here, we used mice to explore the effects of prolonged SD on cardiac structure and function. Echocardiography analysis revealed that cardiac function was significantly decreased in mice after five weeks of SD. Real-time quantitative PCR (RT-q-PCR) and Masson staining analysis showed that cardiac remodeling marker gene Anp (atrial natriuretic peptide) and fibrosis were increased, Elisa assay of serum showed that the levels of creatine kinase (CK), creatine kinase-MB (CK-MB), ANP, brain natriuretic peptide (BNP) and cardiac troponin T (cTn-T) were increased after SD, suggesting that cardiac remodeling and injury occurred. Transcript sequencing analysis indicated that genes involved in the regulation of calcium signaling pathway, dilated cardiomyopathy, and cardiac muscle contraction were changed after SD. Accordingly, Western blotting analysis demonstrated that the cardiac-contraction associated CaMKK2/AMPK/cTNI pathway was inhibited. Since our preliminary research has confirmed the vital role of Casein Kinase-2 -Interacting Protein-1 (CKIP-1, also known as PLEKHO1) in cardiac remodeling regulation. Here, we found the levels of the 3' untranslated region of Ckip-1 (Ckip-1 3'UTR) decreased, while the coding sequence of Ckip-1 (Ckip-1 CDS) remained unchanged after SD. Significantly, adenovirus-mediated overexpression of Ckip-1 3'UTR alleviated SD-induced cardiac dysfunction and remodeling by activating CaMKK2/AMPK/cTNI pathway, which proposed the therapeutic potential of Ckip-1 3'UTR in treating SD-induced heart disease.

睡眠不足(SD)已成为影响人类健康的一个重要问题,会对心血管系统造成严重损害。然而,其潜在机制尚不清楚,靶向药物的开发也相对滞后。在这里,我们用小鼠来探讨长期SD对心脏结构和功能的影响。超声心动图分析表明,小鼠在SD五周后心脏功能明显下降。实时定量 PCR(RT-q-PCR)和 Masson 染色分析表明,心脏重塑标志基因 Anp(心房利钠肽)和纤维化增加、血清中肌酸激酶(CK)、肌酸激酶-MB(CK-MB)、ANP、脑钠肽(BNP)和心肌肌钙蛋白 T(cTn-T)的水平在 SD 后升高,表明心脏发生了重塑和损伤。转录本测序分析表明,参与钙信号通路调控、扩张型心肌病和心肌收缩的基因在 SD 后发生了变化。相应地,Western 印迹分析表明,与心肌收缩相关的 CaMKK2/AMPK/cTNI 通路受到了抑制。我们的初步研究证实了酪蛋白激酶-2-互作蛋白-1(CKIP-1,又称 PLEKHO1)在心脏重塑调控中的重要作用。在此,我们发现SD后Ckip-1的3'非翻译区(Ckip-1 3'UTR)水平下降,而Ckip-1的编码序列(Ckip-1 CDS)保持不变。值得注意的是,腺病毒介导的Ckip-1 3'UTR过表达通过激活CaMKK2/AMPK/cTNI通路缓解了SD诱导的心功能障碍和重塑,这提出了Ckip-1 3'UTR在治疗SD诱导的心脏病方面的治疗潜力。
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引用次数: 0
Signaling pathways in colorectal cancer implications for the target therapies. 结直肠癌信号通路对靶向疗法的影响。
IF 6.3 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-07 DOI: 10.1186/s43556-024-00178-y
Yanlin Song, Ming Chen, Yuhao Wei, Xuelei Ma, Huashan Shi

Colorectal carcinoma (CRC) stands as a pressing global health issue, marked by the unbridled proliferation of immature cells influenced by multifaceted internal and external factors. Numerous studies have explored the intricate mechanisms of tumorigenesis in CRC, with a primary emphasis on signaling pathways, particularly those associated with growth factors and chemokines. However, the sheer diversity of molecular targets introduces complexity into the selection of targeted therapies, posing a significant challenge in achieving treatment precision. The quest for an effective CRC treatment is further complicated by the absence of pathological insights into the mutations or alterations occurring in tumor cells. This study reveals the transfer of signaling from the cell membrane to the nucleus, unveiling recent advancements in this crucial cellular process. By shedding light on this novel dimension, the research enhances our understanding of the molecular intricacies underlying CRC, providing a potential avenue for breakthroughs in targeted therapeutic strategies. In addition, the study comprehensively outlines the potential immune responses incited by the aberrant activation of signaling pathways, with a specific focus on immune cells, cytokines, and their collective impact on the dynamic landscape of drug development. This research not only contributes significantly to advancing CRC treatment and molecular medicine but also lays the groundwork for future breakthroughs and clinical trials, fostering optimism for improved outcomes and refined approaches in combating colorectal carcinoma.

结直肠癌(CRC)是一个紧迫的全球性健康问题,其特点是未成熟细胞在多方面内外因素的影响下肆意增殖。大量研究探索了 CRC 肿瘤发生的复杂机制,主要重点是信号通路,尤其是与生长因子和趋化因子相关的信号通路。然而,分子靶点的多样性给靶向疗法的选择带来了复杂性,给实现精准治疗带来了巨大挑战。由于缺乏对肿瘤细胞突变或改变的病理学洞察,寻找有效的 CRC 治疗方法变得更加复杂。这项研究揭示了从细胞膜到细胞核的信号传递,揭示了这一关键细胞过程的最新进展。通过揭示这一新颖的层面,研究加深了我们对 CRC 潜在的分子复杂性的理解,为靶向治疗策略的突破提供了潜在的途径。此外,该研究还全面概述了信号通路异常激活所引发的潜在免疫反应,重点关注免疫细胞、细胞因子及其对药物开发动态格局的集体影响。这项研究不仅极大地推动了结直肠癌治疗和分子医学的发展,还为未来的突破和临床试验奠定了基础,为改善结直肠癌的治疗效果和改进治疗方法带来了希望。
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引用次数: 0
Signaling pathways in liver cancer: pathogenesis and targeted therapy. 肝癌的信号通路:发病机制和靶向治疗。
IF 6.3 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-05-31 DOI: 10.1186/s43556-024-00184-0
Yangtao Xue, Yeling Ruan, Yali Wang, Peng Xiao, Junjie Xu

Liver cancer remains one of the most prevalent malignancies worldwide with high incidence and mortality rates. Due to its subtle onset, liver cancer is commonly diagnosed at a late stage when surgical interventions are no longer feasible. This situation highlights the critical role of systemic treatments, including targeted therapies, in bettering patient outcomes. Despite numerous studies on the mechanisms underlying liver cancer, tyrosine kinase inhibitors (TKIs) are the only widely used clinical inhibitors, represented by sorafenib, whose clinical application is greatly limited by the phenomenon of drug resistance. Here we show an in-depth discussion of the signaling pathways frequently implicated in liver cancer pathogenesis and the inhibitors targeting these pathways under investigation or already in use in the management of advanced liver cancer. We elucidate the oncogenic roles of these pathways in liver cancer especially hepatocellular carcinoma (HCC), as well as the current state of research on inhibitors respectively. Given that TKIs represent the sole class of targeted therapeutics for liver cancer employed in clinical practice, we have particularly focused on TKIs and the mechanisms of the commonly encountered phenomena of its resistance during HCC treatment. This necessitates the imperative development of innovative targeted strategies and the urgency of overcoming the existing limitations. This review endeavors to shed light on the utilization of targeted therapy in advanced liver cancer, with a vision to improve the unsatisfactory prognostic outlook for those patients.

肝癌是全球最常见的恶性肿瘤之一,发病率和死亡率都很高。由于起病隐匿,肝癌通常在晚期才被确诊,此时手术治疗已不再可行。这种情况凸显了系统治疗(包括靶向治疗)在改善患者预后方面的关键作用。尽管对肝癌的发病机制进行了大量研究,但酪氨酸激酶抑制剂(TKIs)是目前唯一广泛应用于临床的抑制剂,以索拉非尼为代表,其临床应用受到耐药现象的极大限制。在此,我们将深入探讨肝癌发病机制中经常涉及的信号通路,以及针对这些通路正在研究或已用于晚期肝癌治疗的抑制剂。我们分别阐明了这些通路在肝癌尤其是肝细胞癌(HCC)中的致癌作用以及抑制剂的研究现状。鉴于TKIs是目前临床上唯一的肝癌靶向治疗药物,我们特别关注TKIs及其在HCC治疗中常见的耐药现象的机制。这就要求我们必须开发创新的靶向策略,克服现有的局限性。本综述旨在阐明晚期肝癌靶向治疗的应用,以期改善这些患者不尽人意的预后前景。
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引用次数: 0
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Molecular biomedicine
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